Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

SAN FRANCISCO -- Injecting botulinum toxin into the fat pads around the heart after bypass surgery might stave off postoperative atrial fibrillation, a pilot study showed.

Patients who received injections of botulinum toxin instead of a normal saline placebo had a significantly lower rate of atrial tachyarrhythmias -- including atrial fibrillation and atrial flutter/tachycardia -- in the first 30 days (30% versus 7%, P=0.024), according to Evgeny Pokushalov, MD, PhD, of the State Research Institute of Circulation Pathology in Novosibirsk, Russia.

The botulinum toxin treatment was not associated with any complications, with no cases of congestive heart failure, myocardial infarction, stroke, death, and no differences between groups for other outcomes, he reported at the Heart Rhythm Society meeting here.

Pokushalov called the findings "very, very encouraging," and said that "botulinum toxin injection into the epicardial fat pads warrants further investigation as an agent to suppress postoperative atrial fibrillation."

If the results are borne out in a larger multicenter study, he said, "I strongly believe this technique can be [the] gold standard for open heart surgery."

John Day, MD, an electrophysiologist at Intermountain Heart Rhythm Specialists in Utah and program chair for this year's meeting, called the study fascinating, but said that questions remain about the long-term effects of the treatment on atrial fibrillation and about potential adverse consequences.

"This is a very fascinating study, very provocative, but we need more data from other centers looking at this, as well as long-term data," he said.

Even if the effect of botulinum toxin is short-lived, there could be an important benefit because atrial fibrillation that occurs after cardiac surgery -- though also usually short-lived -- is associated with longer stays in the ICU and hospital and increased risks of complications and death.

"This could be a very effective treatment that could be done relatively quickly by the surgeon to help decrease this perioperative atrial fibrillation," Day said.

Atrial fibrillation occurs in 30% to 50% of patients undergoing cardiac surgery, usually in the first 5 days after surgery, although there are not many options to treat it. Guidelines recommend using a beta-blocker, but "all therapeutic options have variable efficacy and some may adversely affect hemodynamic stability," Pokushalov said.

Evidence suggests that the autonomic nervous system plays a role in atrial fibrillation, and ablation of the epicardial fat pads, which contain a rich network of nerves, has been shown to suppress the arrhythmia. In animal models, botulinum toxin injections into the fat pads has temporarily suppressed atrial fibrillation.

To test the approach in humans, Pokushalov and colleagues randomized 60 patients undergoing coronary artery bypass grafting (CABG) to receive injections of incobotulinumtoxin A (Xeomin) administered at 50 U/mL into each of the four major epicardial fat pads or injections of 0.9% normal saline at 1 mL. All patients had a history of paroxysmal atrial fibrillation before surgery, and none had a history of cardiac surgery or ablation procedures.

The patients were continuously monitored with ECG telemetry in the hospital and then with ECGs and 24-hour Holter recordings taken at 7, 14, 21, and 30 days.

Patients in both groups received a similar number of saphenous vein grafts and internal mammary artery grafts during the operation. There were no differences after surgery in the time to begin ventilator weaning, the time to extubation, or the time to discharge from the intensive care unit. The post-CABG length of stay was 6 days in both groups.

Similarly, CK-MB levels did not differ at 1, 8, 16, or 24 hours after the end of cardiopulmonary bypass.

The botulinum toxin injection was associated with a significantly lower rate of atrial tachyarrhythmia recurrence within 30 days, without an increase in any postoperative complications, but Pokushalov acknowledged some limitations of the study, including the small number of patients, the inclusion of patients with prior atrial fibrillation exclusively, and the uncertainty about the long-term effects of botulinum toxin on the maintenance of sinus rhythm.

Outgoing HRS president Hugh Calkins, MD, director of the cardiac arrhythmia service at the Johns Hopkins Hospital in Baltimore, pointed out that postoperative atrial fibrillation is an important problem because it keeps patients in the hospital longer and requires treatment with anticoagulation.

He saw promise in the results presented by Pokushalov.

"If, in fact, at the time of surgery you can squirt some [botulinum toxin] into the four fat pads, and if that is quick and safe and that cuts the amount of [atrial fibrillation] by 75%, I would think that would be a very effective strategy that will catch on widely with all patients getting bypass surgery," Calkins said.

"Obviously it's a proof of concept," he added, "but certainly the data presented speaks to the fact that they need to go to the next step, which is larger trials, more patients, more data."

Calkins said he's not sure what botulinum toxin costs, but "if it adds 5 minutes to surgery and it's safe and it adds $200 to the cost of the procedure and it will get patients out a day or 2 or 3 earlier from the hospital, then it will end up being cost-effective."

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